转录因子 Rfx7 限制 NK 细胞的代谢，促进其维持和免疫。
The transcription factor Rfx7 limits metabolism of NK cells and promotes their maintenance and immunity.
机构信息
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland.
出版信息
Nat Immunol. 2018 Aug;19(8):809-820. doi: 10.1038/s41590-018-0144-9. Epub 2018 Jul 2.
Abstract
Regulatory factor X 7 (Rfx7) is an uncharacterized transcription factor belonging to a family involved in ciliogenesis and immunity. Here, we found that deletion of Rfx7 leads to a decrease in natural killer (NK) cell maintenance and immunity in vivo. Genomic approaches showed that Rfx7 coordinated a transcriptional network controlling cell metabolism. Rfx7 NK lymphocytes presented increased size, granularity, proliferation, and energetic state, whereas genetic reduction of mTOR activity mitigated those defects. Notably, Rfx7-deficient NK lymphocytes were rescued by interleukin 15 through engagement of the Janus kinase (Jak) pathway, thus revealing the importance of this signaling for maintenance of such spontaneously activated NK cells. Rfx7 therefore emerges as a novel transcriptional regulator of NK cell homeostasis and metabolic quiescence.
摘要
调节因子 X7（Rfx7）是一种尚未被描述的转录因子，属于参与纤毛发生和免疫的家族。在这里，我们发现 Rfx7 的缺失导致体内自然杀伤（NK）细胞的维持和免疫能力下降。基因组方法表明，Rfx7 协调了一个转录网络，控制着细胞代谢。Rfx7 NK 淋巴细胞表现出增大、颗粒性增强、增殖和能量状态增加，而雷帕霉素靶蛋白（mTOR）活性的遗传降低减轻了这些缺陷。值得注意的是，通过 Janus 激酶（Jak）途径激活白细胞介素 15 可以拯救 Rfx7 缺陷的 NK 淋巴细胞，从而揭示了这种信号对于维持这种自发激活的 NK 细胞的重要性。因此，Rfx7 成为 NK 细胞动态平衡和代谢静止的新型转录调节因子。
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本文引用的文献
1
Ensembl 2018.Ensembl 2018.
Nucleic Acids Res. 2018 Jan 4;46(D1):D754-D761. doi: 10.1093/nar/gkx1098.
2
mTOR/Raptor signaling is critical for skeletogenesis in mice through the regulation of Runx2 expression.mTOR/Raptor 信号通路通过调节 Runx2 表达对小鼠成骨细胞分化起关键作用。
Cell Death Differ. 2017 Nov;24(11):1886-1899. doi: 10.1038/cdd.2017.110. Epub 2017 Jul 7.
3
UniProt: the universal protein knowledgebase.通用蛋白质知识库：UniProt
Nucleic Acids Res. 2017 Jan 4;45(D1):D158-D169. doi: 10.1093/nar/gkw1099. Epub 2016 Nov 29.
4
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Nat Commun. 2016 Sep 7;7:12730. doi: 10.1038/ncomms12730.
5
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6
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J Immunol. 2016 May 1;196(9):3537-41. doi: 10.4049/jimmunol.1501896. Epub 2016 Mar 21.
7
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J Immunol. 2016 Apr 1;196(7):2939-46. doi: 10.4049/jimmunol.1502084. Epub 2016 Mar 4.
8
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9
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10
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